Erythrinian alkaloids from Erythrina mulungu Mart. ex Benth: general and comparative neurochemical, imunohistochemical, molecular and neuroethological analysis in rats submitted to pilocarpine seizure-induced model

Abstract

Temporal Lobe Epilepsy (TLE) is responsible for 40% of diagnosed cases of epilepsy. This type of epilepsy is in general of difficult treatment and the current therapy is characterized by occurrence of several side effects such as sedation, cognition deficit and chemical dependence, which led to partial or total impairment of patients to work. Therefore, the search of new antiepileptic drugs (AEDs) is of relevance to understanding of this neurological disorder and also for a better treatment of patients. Based on ethnopharmacological data, several medicinal plants have been studied for their pharmacological actions against epilepsy, anxiety and for cerebral protection. The plant Erythrina mulungu Mart. ex Benth. (Leguminosae-Papilionaceae) has been used in the folk medicine and also in industrial phytoterapical preparations due to its sedative, anticonvulsant, hypnotic and anxiolytic properties. Indeed, recent reports have pointed to marked anticonvulsant and anxiolytic effects of E. mulungu flower and leaf hidroalcoolic extract in different animal models of epilepsy. Those effects have been attributed to the presence of (+)-erythravine, (+)-11-±-hidroxi-erythravine and/or eryysothrine alkaloids isolated from the plant. Previous results of our research group have showed that different i.c.v doses of those alkaloids are able to inhibited acute seizures evoked by bicuculline, PTZ, NMDA and kainic acid. Moreover, these alkaloids have been showed to be responsible for anxiolytic effects of E. mulungu in Elevated Plus Maze, Light-Dark Choice Box and Open-Field tests. However, no experimental approach has been used to evaluate the anticonvulsant effects of these alkaloids in a chronic animal model of epilepsy. This approach is important to a better understanding of a mode of action of those alkaloids and also in terms of recurrence of seizures and development of epileptogenesis process in presence or absence of these alkaloids in treated animals. Although previous efforts of our group only discrete information are know about the molecular targets of these alkaloids when evoking their anticonvulsant effects in brain. Thus this work aim in evaluate the effects of (+)-erythravine, (+)-11-±-hidroxi-erythravine and eryysothrine alkaloids on animal neuroprotection when rats are submitted to the chronic experimental model of epilepsy using pilocarpine, a chemical inducer of status epilepticus. It will be evaluated the anticonvulsant effects of alkaloids in general or in comparison to the conventional AEDs using neuroethological, histological and imunohistochemical parameters of analysis. Also, differential expression of GABAA and NMDA receptors will be evaluated among hippocampus from control and experimental animals by use of Real time PCR. To continuous our previous Fapesp research project (2009/11357-1) a new approach to investigate the actions of these alkaloids on GABAergic (BZP-site) and Glutamatergic (NMDA-site) receptors will be performed using a neurochemical experimental setup. (AU)